Astrocytomas are members of the glioma family of tumors; that is, tumors arising from glial cells. In the case of astrocytomas, the tumors arise from a type of glial cell called astrocytes.
Astrocytes, named by Spanish neuroanatomist Santiago Ramon y Cajal in 1913 after he discovered the star-shaped cells, are the major cell types of the central nervous system that responds to various pathological conditions, including trauma, ischemia, demylination, inflammation, etc. In response to such pathological conditions, the normally quiescent astrocyte becomes “reactive,” and may proliferate and migrate, exhibiting hypertrophy with increased expression of Glial Fibrillary Acidic Protein (GFAP), expression of cell surface MHC class I and II molecules, and producing various cytokines and growth factors.
Neoplastic transformation of astrocytes give rise to a variety of astrocytomas. Astrocytomas are generally grouped into two categories: low-grade (grades 1 and 2) and high-grade (grades 3 and 4). High-grade tumors grow rapidly and can easily spread throughout the brain, while low-grade astrocytomas are usually much more localized and grow slowly over a longer period of time. The prognosis for patients with high-grade astrocytomas is poor, with an average survival of 18 months for patients with grade 3 astrocytoma (with radiation therapy and chemotherapy) and an average survival of from 17 weeks (no treatment) to 51 weeks (with surgery and radiation treatment) for grade 4 astrocytomas.
Morphologically, low-grade astrocytomas are usually normal in appearance, making it difficult to distinguish low-grade astrocytoma cells from normal quiescent or reactive cells. Some grade 2 low-grade astrocytomas may be slightly abnormal in appearance, but are not easily detected by routine microscopic evaluation of tissue biopsy samples. By contrast, the high-grade astrocytomas are abnormal in appearance and show evidence of mitosis, making the cells easily identifiable by microscopic evaluation.
Visualization of astrocytes during microscopic evaluation of tissue sections is typically facilitated by staining the biopsy tissue sample with antibody to GFAP, a cytoskeletal protein expressed both in quiescent and reactive astrocytes and in low grade and high grade astrocytomas. Both monoclonal mouse and polyclonal rabbit anti-human GFAP antibodies have been developed that are specific against GFAP, not recognizing other intermediate filament proteins. These antibodies typically react with both astrocytes and astrocytoma cells, and thus do not serve to differentiate between normal and transformed cells beyond facilitating morphological inspection
Although the prognosis for patients with grade 1 astrocytoma is good, with some patients known to live 30 years or more following diagnosis, the prognosis for patients with grade 2 low-grade astrocytoma is much less optimistic. Recent studies have indicated that the 5-year survival rate in grade 2 astrocytomas is about 34%. With radiation therapy, the 5-year survival rate increased to about 70%. It is apparent that early diagnosis, and thus early treatment, is important in treating patients with low-grade astrocytoma.
What is needed, therefore, is a reliable and efficient diagnostic procedure for differentiating low grade astrocytoma cells from active and quiescent normal astrocytes in tissue biopsies.